The candidate, Dr. Christina Lessov-Schlaggar, seeks support for 5 years through this Mentored Research Scientist Development Award (K01) in order to (1) obtain training in functional neuroimaging to complement her training in psychiatric genetics of tobacco use etiology; (2) gain understanding of developmental cognitive neuroscience to enhance knowledge and guide current and future investigation of tobacco use etiology; and (3) improve statistical skills for longitudinal data analysis. This proposal will prepare the applicant to establish an independent research program to understand neural and cognitive mechanisms of addiction development using genetic and neuroimaging approaches. This goal will be achieved through (i) secondary data analysis of developmental smoking trajectories and their relationship to tobacco dependence in a genetically informative sample of twins, and (ii) functional neuroimaging pilot data collection in a subset of the same twin sample to examine brain activation differences in addiction-related regions between regular and non-regular smokers. The functional neuroimaging pilot study will employ a co-twin control design which allows investigation of the effects of regular smoking on neural processing, unconfounded by genetic and family background factors. Since smoking trajectory and neuroimaging data will be available from the same individuals, brain activation differences can be mapped onto differences in smoking trajectories, which will serve as one reference point for subject selection and study design for future R01 applications. This proposal describes a comprehensive and focused training program that includes formal coursework, supervised self-directed learning and hands-on training in one of the nation's leading academic institutions and under the guidance of leaders in the fields of functional neuroimaging (Dr. Deanna Barch, mentor; Dr. Steven Petersen, co-mentor), genetics of tobacco use etiology (Dr. Pamela Madden, co-mentor), and behavioral genetics (Dr. Andrew Heath, consultant). PUBLIC HEALTH RELEVANCE: Cigarette smoking is the single, most preventable cause of lung cancer and is a significant source of morbidity and mortality worldwide. Improved understanding of brain and cognitive mechanisms of tobacco dependence and its development will contribute to better, potentially individually-tailored, prevention, intervention, and treatment approaches.